Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies (Unite-CNM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT04033159

Recruitment Status : Terminated (Based on tolerability findings at the low dose level thus far, continuation of dosing or even dose escalation is not possible.)

First Posted : July 25, 2019

Results First Posted : June 27, 2023

Last Update Posted : June 27, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Dynacure

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Centronuclear Myopathy
Intervention	Drug: DYN101
Enrollment	14

Participant Flow

Recruitment Details
Pre-assignment Details	No participant was enrolled in the "Cohort 3 - High Dose" Arm/Group


Arm/Group Title	Cohort 1 - Low Dose	Cohort 2 - Middle Dose	Cohort 3 - High Dose
Arm/Group Description	DYN101 in a low dose (1.5 mg/kg wee...	DYN101 in a middle dose (4.5 mg/kg ...	DYN101 in a high dose (9 mg/kg week...
Arm/Group Description	DYN101 in a low dose (1.5 mg/kg weekly IV)	DYN101 in a middle dose (4.5 mg/kg weekly IV)	DYN101 in a high dose (9 mg/kg weekly IV)
Period Title: Single Ascending Dose (Day 1)
Started	6	8	0
Completed	6	8	0
Not Completed	0	0	0
Period Title: Washout Period
Started	6	8	0
Completed	6	0	0
Not Completed	0	8	0
Reason Not Completed
Physician Decision	0	1	0
Study terminated by Sponsor	0	7	0
Period Title: Multiple Ascending Dose Period
Started	6	0	0
Completed	0	0	0
Not Completed	6	0	0
Reason Not Completed
Study terminated by Sponsor	6	0	0

Baseline Characteristics

Arm/Group Title		Cohort 1 - Low Dose	Cohort 2 - Middle Dose	Total
Arm/Group Description		DYN101 in a low dose (1.5 mg/kg)	DYN101 in a middle dose (4.5 mg/kg)	Total of all reporting groups
Arm/Group Description		DYN101 in a low dose (1.5 mg/kg)	DYN101 in a middle dose (4.5 mg/kg)	Total of all reporting groups
Overall Number of Baseline Participants		6	8	14
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	6 participants	8 participants	14 participants
		39.8 (16.49)	37.4 (16.80)	38.4 (16.07)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	8 participants	14 participants
	Female	2 33.3%	4 50.0%	6 42.9%
	Male	4 66.7%	4 50.0%	8 57.1%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	8 participants	14 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	6 100.0%	8 100.0%	14 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	8 participants	14 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	5 83.3%	7 87.5%	12 85.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 16.7%	1 12.5%	2 14.3%
Mutation Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	8 participants	14 participants
	DNM2	3 50.0%	5 62.5%	8 57.1%
	MTM1	3 50.0%	3 37.5%	6 42.9%

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Drug-related Treatment Emergent Adverse Events (TEAEs)
Description	Number of participants with drug-related TEAEs during the study period...
Description	Number of participants with drug-related TEAEs during the study period.
Time Frame	Baseline until Study termination, up to 28 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Single Dose Cohort 1 - Low Dose	Single Dose Cohort 2 - Middle Dose	Multiple Dose Cohort 1 - Low Dose
Arm/Group Description:	DYN101 in a low dose (1.5 mg/kg), s...	DYN101 in a middle dose (4.5 mg/kg)...	DYN101 in a low dose (1.5 mg/kg), w...
Arm/Group Description:	DYN101 in a low dose (1.5 mg/kg), single administration	DYN101 in a middle dose (4.5 mg/kg), single administration	DYN101 in a low dose (1.5 mg/kg), weekly administration
Overall Number of Participants Analyzed	6	8	6
Measure Type: Count of Participants Unit of Measure: Participants
	1 16.7%	5 62.5%	6 100.0%

Adverse Events

Time Frame	Baseline until Study termination, up to 28 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Single Dose Cohort 1 - Low Dose		Single Dose Cohort 2 - Middle Dose		Multiple Dose Cohort 1 - Low Dose
Arm/Group Description	DYN101 in a low dose (1.5 mg/kg), s...		DYN101 in a middle dose (4.5 mg/kg)...		DYN101 in a low dose (1.5 mg/kg), w...
Arm/Group Description	DYN101 in a low dose (1.5 mg/kg), single administration		DYN101 in a middle dose (4.5 mg/kg), single administration		DYN101 in a low dose (1.5 mg/kg), weekly administration
All-Cause Mortality
	Single Dose Cohort 1 - Low Dose		Single Dose Cohort 2 - Middle Dose		Multiple Dose Cohort 1 - Low Dose
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/6 (0.00%)		0/8 (0.00%)		0/6 (0.00%)
Serious Adverse Events Serious Adverse Events
	Single Dose Cohort 1 - Low Dose		Single Dose Cohort 2 - Middle Dose		Multiple Dose Cohort 1 - Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50.00%)		2/8 (25.00%)		0/6 (0.00%)
Ear and labyrinth disorders
Cholesteatoma ^†	1/6 (16.67%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
Tibia fracture ^†	0/6 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast mass ^†	1/6 (16.67%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
COVID-19 ^†	1/6 (16.67%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0
Respiratory muscle weakness ^†	0/6 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Single Dose Cohort 1 - Low Dose		Single Dose Cohort 2 - Middle Dose		Multiple Dose Cohort 1 - Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100.00%)		8/8 (100.00%)		6/6 (100.00%)
Blood and lymphatic system disorders
Anaemia ^†	0/6 (0.00%)		1/8 (12.50%)		1/6 (16.67%)
Thrombocytopenia ^†	0/6 (0.00%)		1/8 (12.50%)		5/6 (83.33%)
Leukopenia ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Cardiac disorders
Arrhythmia ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Palpitations ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Tachycardia ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Ear and labyrinth disorders
Vertigo ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Gastrointestinal disorders
Abdominal pain ^†	2/6 (33.33%)		4/8 (50.00%)		1/6 (16.67%)
Abdominal pain upper ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Nausea ^†	1/6 (16.67%)		3/8 (37.50%)		1/6 (16.67%)
Oral mucosal discolouration ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Palatal disorder ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Toothache ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Hypoaesthesia oral ^†	0/6 (0.00%)		0/8 (0.00%)		2/6 (33.33%)
Diarrhoea ^†	0/6 (0.00%)		0/8 (0.00%)		2/6 (33.33%)
General disorders
Chest pain ^†	2/6 (33.33%)		2/8 (25.00%)		0/6 (0.00%)
Eye complication associated with device ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Fatigue ^†	0/6 (0.00%)		2/8 (25.00%)		1/6 (16.67%)
Vessel puncture site bruise ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Hepatobiliary disorders
Hepatic fibrosis ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Immune system disorders
Immunisation reaction ^†	2/6 (33.33%)		0/8 (0.00%)		0/6 (0.00%)
Infections and infestations
COVID-19 ^†	2/6 (33.33%)		0/8 (0.00%)		1/6 (16.67%)
Cystitis ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Nasopharyngitis ^†	2/6 (33.33%)		0/8 (0.00%)		0/6 (0.00%)
Pyelonephritis ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Sinusitis ^†	2/6 (33.33%)		0/8 (0.00%)		0/6 (0.00%)
Viral infection ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Injury, poisoning and procedural complications
Ankle fracture ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Fall ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Foot fracture ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Post procedural haematoma ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Procedural pain ^†	1/6 (16.67%)		0/8 (0.00%)		1/6 (16.67%)
Upper limb fracture ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Investigations
Blood bilirubin increased ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
C-reactive protein increased ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Hepatic enzyme increased ^†	0/6 (0.00%)		2/8 (25.00%)		2/6 (33.33%)
Red blood cells urine positive ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Transaminases increased ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Alanine aminotransferase increased ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Aspartate aminotransferase increased ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Cystatin C increased ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Gamma-glutamyltransferase increased ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Liver function test increased ^†	0/6 (0.00%)		0/8 (0.00%)		3/6 (50.00%)
Total bile acids increased ^†	0/6 (0.00%)		0/8 (0.00%)		2/6 (33.33%)
Dizziness ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Back pain ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Joint swelling ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Myalgia ^†	2/6 (33.33%)		0/8 (0.00%)		1/6 (16.67%)
Pain in extremity ^†	2/6 (33.33%)		1/8 (12.50%)		0/6 (0.00%)
Neck pain ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Nervous system disorders
Disturbance in attention ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Headache ^†	2/6 (33.33%)		3/8 (37.50%)		2/6 (33.33%)
Hypoaesthesia ^†	0/6 (0.00%)		1/8 (12.50%)		1/6 (16.67%)
Neuralgia ^†	2/6 (33.33%)		0/8 (0.00%)		0/6 (0.00%)
Anxiety ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Sleep disorder ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Paraesthesia ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Tension headache ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Psychiatric disorders
Depression ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Renal and urinary disorders
Haematuria ^†	0/6 (0.00%)		1/8 (12.50%)		1/6 (16.67%)
Nephrolithiasis ^†	0/6 (0.00%)		0/8 (0.00%)		1/6 (16.67%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Skin and subcutaneous tissue disorders
Hyperhidrosis ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
Rash ^†	1/6 (16.67%)		0/8 (0.00%)		0/6 (0.00%)
Vascular disorders
Circulatory collapse ^†	0/6 (0.00%)		1/8 (12.50%)		0/6 (0.00%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dynacure
Organization:	Dynacure
Phone:	+33 3 74 95 20 50
EMail:	info@dynacure.com

Layout table for additonal information

Responsible Party:	Dynacure
ClinicalTrials.gov Identifier:	NCT04033159
Other Study ID Numbers:	DYN101-C101
First Submitted:	June 12, 2019
First Posted:	July 25, 2019
Results First Submitted:	March 23, 2023
Results First Posted:	June 27, 2023
Last Update Posted:	June 27, 2023

To Top